Rates of Response to Atogepant for Migraine Prophylaxis Among Adults
Authors: Richard B. Lipton, Patricia Pozo-Rosich, Andrew M. Blumenfeld, David W. Dodick, Peter McAllister, Ye Li, Kaifeng Lu, Brett Dabruzzo, Rosa Miceli, Lawrence Severt, Michelle Finnegan, Joel M. Trugman
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Some patients with migraine, particularly those in primary care, require effective, well-tolerated, migraine-specific oral preventive treatments. <h3>Objective</h3> To examine the efficacy of atogepant, an oral, small-molecule, calcitonin gene–related peptide receptor antagonist, using 4 levels of mean monthly migraine-day (MMD) responder rates. <h3>Design, Setting, and Participants</h3> This secondary analysis of a phase 3, double-blind, placebo-controlled randomized clinical trial evaluated the efficacy and safety of atogepant for the preventive treatment of migraine from December 14, 2018, to June 19, 2020, in adults with 4 to 14 migraine-days per month at 128 sites in the US. <h3>Interventions</h3> Patients were administered 10 mg of atogepant (n = 222), 30 mg of atogepant (n = 230), 60 mg of atogepant (n = 235), or placebo (n = 223) once daily in a 1:1:1:1 ratio for 12 weeks. <h3>Main Outcomes and Measures</h3> These analyses evaluated treatment responder rates, defined as participants achieving 50% or greater (α-controlled, secondary end point) and 25% or greater, 75% or greater, and 100% (prespecified additional end points) reductions in mean MMDs during the 12-week blinded treatment period. <h3>Results</h3> Of 902 participants (mean [SD] age, 41.6 [12.3] years; 801 [88.8%] female; 752 [83.4%] White; 825 [91.5%] non-Hispanic), 873 were included in the modified intention-to-treat population (placebo, 214; 10 mg of atogepant, 214; 30 mg of atogepant, 223; and 60 mg of atogepant, 222). For the secondary end point, a 50% or greater reduction in the 12-week mean of MMDs was achieved by 119 of 214 participants (55.6%) treated with 10 mg of atogepant (odds ratio, 3.1; 95% CI, 2.1-4.6), 131 of 223 participants (58.7%) treated with 30 mg atogepant (odds ratio, 3.5; 95% CI, 2.4-5.3), 135 of 222 participants (60.8%) treated with 60 mg of atogepant (odds ratio, 3.8; 95% CI, 2.6-5.7), and 62 of 214 participants (29.0%) given placebo (<i>P</i> &lt; .001). The numbers of participants who reported a 25% or greater reduction in the 12-week mean of MMDs were 157 of 214 (73.4%) for 10 mg of atogepant, 172 of 223 (77.1%) for 30 mg of atogepant, and 180 of 222 (81.1%) for 60 mg of atogepant vs 126 of 214 (58.9%) for placebo (<i>P</i> &lt; .002). The numbers of participants who reported a 75% or greater reduction in mean MMDs were 65 of 214 (30.4%) for 10 mg of atogepant, 66 of 223 (29.6%) for 30 mg of atogepant, and 84 of 222 (37.8%) for 60 mg of atogepant compared with 23 of 214 (10.7%) for placebo (<i>P</i> &lt; .001). The numbers of participants reporting 100% reduction in mean MMDs were 17 of 214 (7.9%) for 10 mg of atogepant (<i>P</i> = .004), 11 of 223 (4.9%) for 30 mg of atogepant (<i>P</i> = .02), and 17 of 222 (7.7%) for 60 mg of atogepant (<i>P</i> = .003) compared with 2 of 214 (0.9%) for placebo. <h3>Conclusions and Relevance</h3> At all doses, atogepant was effective during the 12-week double-blind treatment period beginning in the first 4 weeks, as evidenced by significant reductions in mean MMDs at every responder threshold level. Higher atogepant doses appeared to produce the greatest responder rates, which can guide clinicians in individualizing starting doses. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03777059